Description of the Prior Art
Ryan, U.S. Pat. No. 3,641,021, describes the broad spectrum antibiotic cefamandole and its salts such as the sodium salt. Cefamandole has the chemical name 7-(D-.alpha.-hydroxy-.alpha.-phenylacetamido)-3-(1-methyl-1H-tetrazol-5-yl thiomethyl)-3-cephem-4-carboxylic acid or, alternatively, 7-D-mandelamido-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxy lic acid. Ryan also describes the formyl ester of cefamandole, 7-(D-.alpha.-formyloxy-.alpha.-phenylacetamido)-3-(1methyl-1H-tetrazol-5-y lthiomethyl)-3-cephem-4-carboxylic acid. This formate ester formed with the .alpha.-hydroxy group of the 7-position side chain is described by Ryan as an intermediate in the synthesis of cefamandole.
Greene and Indelicato, U.S. Pat. No. 3,928,592, disclose the sodium salt of the formate ester of cefamandole, known as O-formylcefamandole, as a useful pro-drug of cefamandole and describe pharmaceutical formulations useful for parenteral administration. O-Formylcefamandole is described as a stable, crystalline compound which, in contrast with cefamandole itself, is readily purified.
Yang, U.S. Pat. No. 4,006,138, describes the crystalline anhydrate form of O-formylcefamandole sodium designated as the gamma crystalline form, which is stable under conditions of relatively high atmospheric moisture. Yang, U.S. Pat. No. 4,054,738, also describes the new anhydrate, monohydrate and methanolate crystalline forms of sodium cefamandole and their interconversion.
J. M. Indelicato, et al., Journal of the Pharmaceutical Sciences, 65, [8], 1175-1178, (1976) reports studies of the hydrolysis rate of sodium O-formylcefamandole.